full access: Journal of Ovarian Research BRCA1/2 genetic background-based therapeutic tailoring of human ovarian cancer : hope or reality?

Conclusion:
All together these findings introduce a provocative novel scenario where BRCA1/2 carcinogenetic process in the hereditary setting produces novel opportunities for pharmacological intervention. Apart novel drugs like PARP inhibitors, these findings may allow a different and more rational approach for the treatment of BRCA1/2 related ovarian tumors by currently available drugs.
The study by Tan et al[46] clearly demonstrates that CDDP resistance in BRCA1/2-related tumors is a late event and patients experience a long treatment free interval after CDDP-based treatment. The common finding that paclitaxel appear less effective in preclinical models of BRCA1/2 models would suggest a more rational first line treatment with CDDP/gemcitabine combination or even with carboplatin escalated doses in order to achieve the maximal benefit in advance of the occurrence of escape mutations like those recently described in BRCA2 gene.
All these approaches need of course to be explored in well designed prospective clinical trials. The finding by Quinn et al[31] and by Carser et al. [33] that low BRCA1 mRNA and protein expression is predictive of specific benefit of platinum based chemotherapy, while high BRCA1 mRNA might predict for benefit of taxane treatment, might allow to explore the potential advantage of molecular marker-based treatment assignment compared to conventional assignment. This topic is prospectively evaluated in non small cell lung cancer (NSCLC) by Rosell and coworkers[29,30,57]. Treatment tailoring of ovarian cancer on the genetic background appears now to be based on a robust rationale from preclinical and clinical evidence and it is time to undergo evaluation in well designed prospective trials.